Cancer is a class of diseases in which a group of cells display uncontrolled growth and division beyond the normal limits, invasion into and destruction of adjacent tissues, and sometimes metastasis that spreads the cancer to other locations in the body via lymphatics or blood vessels. These malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age. Cancer causes about 13% of all deaths. According to the American Cancer Society, 7.6 million people died from cancer in the U.S. during 2007. Cancers can affect all animals.
Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers are usually affected by complex interactions between carcinogens and the host's genome.
Diagnosis usually requires the histological examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy, and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histological grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.
Cisplatin (i.e., cis-diamminedichloroplatinum or CDDP) has become an important chemotherapeutic agent for many solid tumors. However, newer platinum drugs have been found to have fewer side-effects, and such drugs may become important chemotherapeutic agents. One drawback to cisplatin as well as other chemotherapeutics or potential chemotherapeutics is significant toxicity.
Since organ toxicities hamper chemotherapy, oncologists have developed procedures to confine chemotherapy to the diseased areas by temporarily isolating the affected tissues or organs from the systemic circulation and perfusing them with the chemotherapeutic. For example, intra-arterial percutaneous pelvic perfusion of high-dose chemotherapeutic can provide a therapeutic advantage in advanced uterine cervical carcinoma with low side effects. However, these treatments are highly invasive and require specialized skills and equipment usually restricted to large medical research centers. In addition, tissue isolation is not possible in many cases, including locally advanced breast cancer that has significant invasion into lymphatic tissues.
Treatment of locally advanced breast cancer may be improved if chemotherapy were concentrated to the breast lymphatics, while maintaining adequate systemic levels for treatment of distant metastases. Neoadjuvant systemic chemotherapy is standard care for locally advanced breast cancer (LABC), but after treatment cancer typically spreads first via the lymphatics with little stroma invasion before becoming a systemic disease. Surgical treatment for early stage breast cancer involves resection of the primary tumor along with the draining sentinel lymph node and further lymphatic resection if warranted. However, this procedure may miss nanoscopic metastases in the lymph nodes if full immunohistochemical analysis is not routinely performed on sentinel node specimens, which is estimated to double the risk of relapse (compared to truly node negative cases). Localized radiation to the breast and lymphatics along with systemic chemotherapy reduce the risks of relapse, but these treatments cause extensive damage to healthy tissues.
Regardless of their origin, many cancers metastasize by using the lymphatic system (e.g. breast, ovarian, melanoma). The lymphatics are the body's drainage system, clearing waste from the tissues, and metastatic cancers follow this drainage to “seed” first in the local lymphatics. Surgery and chemotherapy can destroy many of these early metastases, but with great morbidity to the patient (e.g. toxicity side effects and painful lymphedema). Thus, it would be beneficial to have a chemotherapeutic that avoids these side effects by delivering chemotherapy directly to the tumor tissue in early cancers. Also, it would be advantageous for a chemotherapeutic to be preferentially directed into the lymphatics, and thereby avoiding side effects on normal cells elsewhere in the body, destroying the “seeds” that can cause recurrence after surgery and whole-body chemotherapy.